title: No extreme genetic risk for type 1 diabetes among DR3/4-DQ8 siblings sharing both extended HLA haplotypes with their diabetic proband.
abstract: An extreme genetic risk for type 1 diabetes (T1D) was reported for DR3/4-DQ8 siblings sharing both extended human leukocyte antigen (HLA) haplotypes identical-by-descent (IBD) with their diabetic proband. We attempted to replicate this finding in our prospective Dutch T1D cohort and in families from the Type 1 Diabetes Genetics Consortium (T1DGC). Only 2 of the 14 Dutch siblings, sharing both DR3-DQ2/DR4-DQ8 haplotypes IBD with their diabetic proband, developed T1D in a 12-year follow-up period. No differential sharing of HLA haplotypes or significant transmission distortion in parents homozygous for HLA risk alleles was found in T1DGC material. Therefore, we could not confirm the reported extreme risk for T1D, suggesting that the risk conferred by other HLA complex loci is moderate.
authors.affiliation: Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Eerligh
authors.forename: B P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: E
authors.initials: E
authors.lastname: Thorsby
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens; D015803:HLA-DR3 Antigen / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009426:Netherlands; D012307:Risk Factors; D035781:Siblings
chemical_list: D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen